The Effects of Salvia miltiorrhiza and Silymarin on CBDL Induced Oxidative Damage and Mitochondrial Dysfunction in Cirrhotic Rats.

• Main Authors: Chi-Jen Chen, 陳麒任
• Other Authors: Yi-Tsau Huang
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/94233838877918450979

碩士 === 國立陽明大學 === 傳統醫藥學研究所 === 89 === Abstract Liver cirrhosis is a leading cause of morbidity and mortality in the population of Taiwan. Cirrhosis is pathologically caused by “liver fibrogenesis”, which is a dynamic, complex, progressive, and at some stages, reversible and potentially amenable to drug treatment. Cirrhotic patients and animals are associated with mitochondrial dysfunction and oxidative damage. Long-term common bile duct ligation (CBDL) in the rat is a frequently used experimental model of liver cirrhosis with cholestasis and is associated with mitochondrial dysfunctions. Both Salvia miltiorrhiza and silymarin, an extract from Silybum marianum (L.), have been reported to inhibit lipid peroxidation and possess free radical scavenging activity. The purpose of the study was to investigate the possible changes of oxidative stress induced mitochondrial respiratory dysfunction in liver cirrhosis and to study the effects of Salvia miltiorrhiza and silymarin on mitochondrial dysfunction and oxidative damage in the rat liver. Cirrhosis was induced by CBDL in Sprague-Dawley rats. Sham-operated (sham) rats served as control. In part I of this study, mitochondrial functions were investigated in the CBDL-vehicle group and sham-vehicle group at 15 and 28 days after bile duct ligation. In part II study, effects of herbs on oxidative damage of cirrhotic rats were investigated. There were five groups in this study: CBDL-vehicle group, sham-vehicle group, and CBDL-silymarin (30 mg/kg/bid, p.o.) or CBDL-high dose of Salvia miltiorrhiza (100 mg/kg/bid, p.o.) or CBDL-low dose of Salvia miltiorrhiza (30 mg/kg/bid, p.o.) at 28 days after ligation. The levels of MDA and 8-OHdG/105 dG were measured as indicators of oxidative damage to lipids and DNA, respectively. The redox system of glutathione was used as the index for oxidative stress. The results showed that MDA levels in mitochondria were not significantly different between CBDL and sham rats. MDA levels in plasma were significantly increased (+25% as determined by spectrophotometry; +95.5% as determined by HPLC) in CBDL rats in a time-dependent manner. 8-OHdG/105 dG levels in liver tissue were increased (+40.1%) in CBDL rats. Total glutathione in plasma was decreased (-70.6%) in CBDL rats. On the other hand, we found that Salvia miltiorrhiza treatment could not reduce the plasma MDA levels in CBDL-rats in all groups. By contrast, silymarin could significantly reduce (-17.5%) the plasma MDA levels of CBDL-rats as determined by HPLC. In conclusion, there were oxidative damage to lipids and DNA and derangements of the enzyme activities of mitochondrial electron transport chain in CBDL rats. Moreover, the antioxidant system was diminished in cirrhotic rats. We also found that Salvia miltiorrhiza treatment could not reduce oxidative damage in cirrhotic rats, and that silymarin treatment could ameliorate lipid peroxidation in cirrhotic rats.